The overall goal of these studies is to gain further insight into the role of second receptors during primate immunodeficiency virus entry into cells. The experimental goals are broken down into four categories. In the first set of experiments, the interaction between HIV-1 gp120 and various second receptors will be studied. These studies involve extensive mutagenesis of gp120, CKR5 and fusin. The second Aim is to clone and characterize the second receptors for HIV-2 and non human primate immunodeficiency viruses from chimpanzee, macaque and mangabey as well as from human PBMC. The third Aim will evaluate the ability of HIV strains from different subtypes to utilize different second receptors. The fourth Aim is to understand whether and how variation in the second receptor expression patterns in macrophages and lymphocytes influences HIV-1 entry into these cells; variations in the sensitivity of infection to blocking by b-chemokines will also be examined.